Translational Research Network Research Articles

Changes in systemic cancer therapy in Australia during the COVID-19 pandemic: a population-based study.

BackgroundSince the emergence of COVID-19 there have been increasing global concerns about delays and/or discontinuations in cancer care. However, it is unclear to what extent systemic cancer therapy was impacted by COVID-19 in countries with relatively low COVID-19 infection rates. We examined changes in systemic cancer therapy in Australia during the COVID-19 pandemic.MethodsWe conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between January 2017 to December 2020. We reported monthly dispensing and initiation rates of antineoplastic (chemo-, immuno- and targeted therapy), endocrine and supportive medicines per 100,000 population. We reported monthly discontinuation rates (defined as ≥90 days gap between cancer medicine dispensings) per 1,000 people treated. We used interrupted time series analysis to examine changes during times of increased COVID-19 risk and related public health measures (March, April and July 2020).FindingsBetween January 2017 and December 2020, 1,011,255 cancer medicines were dispensed to 51,515 people. Overall, there were no reductions in antineoplastic dispensing or initiation during the COVID-19 pandemic. In March 2020, we observed a temporary increase of 39/100,000 (95% CI: 14 to 65/100,000) in antineoplastic dispensing, driven by immunotherapy and targeted therapy. In April 2020, we observed a temporary decrease in chemotherapy initiation (-2/100,000, 95% CI: -4 to -1/100,000) and temporary increase in discontinuation of all antineoplastic medicines (35/1,000, 95% CI: 20 to 51/1,000), but these changes were not sustained.InterpretationThe effective control of COVID-19 in Australia appears to have mitigated the initial impact of COVID-19 on systemic cancer therapy. We observed only small and temporary changes in the use of some cancer medicines early in the pandemic.FundingNational Health and Medical Research Council; National Breast Cancer Foundation; Translational Cancer Research Network, supported by the Cancer Institute NSW.

The Longitudinal Pediatric Data Resource: Facilitating Longitudinal Collection of Health Information to Inform Clinical Care and Guide Newborn Screening Efforts

The goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2200 with a range from 69 to 7944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of discoveries into clinical practice.

MAGICPL: A Generic Process Description Language for Distributed Pseudonymization Scenarios.

Pseudonymization is an important aspect of projects dealing with sensitive patient data. Most projects build their own specialized, hard-coded, solutions. However, these overlap in many aspects of their functionality. As any re-implementation binds resources, we would like to propose a solution that facilitates and encourages the reuse of existing components. We analyzed already-established data protection concepts to gain an insight into their common features and the ways in which their components were linked together. We found that we could represent these pseudonymization processes with a simple descriptive language, which we have called MAGICPL, plus a relatively small set of components. We designed MAGICPL as an XML-based language, to make it human-readable and accessible to nonprogrammers. Additionally, a prototype implementation of the components was written in Java. MAGICPL makes it possible to reference the components using their class names, making it easy to extend or exchange the component set. Furthermore, there is a simple HTTP application programming interface (API) that runs the tasks and allows other systems to communicate with the pseudonymization process. MAGICPL has been used in at least three projects, including the re-implementation of the pseudonymization process of the German Cancer Consortium, clinical data flows in a large-scale translational research network (National Network Genomic Medicine), and for our own institute's pseudonymization service. Putting our solution into productive use at both our own institute and at our partner sites facilitated a reduction in the time and effort required to build pseudonymization pipelines in medical research.

EP545 - Piloting newborn screening for neuromuscular disease with data collection tools developed by the Newborn Screening Translational Research Network

eP545 - Piloting newborn screening for neuromuscular disease with data collection tools developed by the Newborn Screening Translational Research Network

EP522 - The Newborn Screening Translational Research Network: accelerating the nomination of new conditions through newborn screening pilot studies

eP522 - The Newborn Screening Translational Research Network: accelerating the nomination of new conditions through newborn screening pilot studies

EP462 - Newborn Screening Translational Research Network: translating evidence-based practices to enhance parent engagement

eP462 - Newborn Screening Translational Research Network: translating evidence-based practices to enhance parent engagement

79602 Designing and Implementing an Assessment of Collaboration for a Clinical and Translational Research Community Advisory Board

ABSTRACT IMPACT: This abstract presents a generalizable process to evaluate, and act on, community advisory board perceptions of collaboration effectiveness to improve clinical and translational research network function. OBJECTIVES/GOALS: Community advisory boards (CAB) play an important role in facilitating relevant and externally valid, clinical and translational research (CTR). The objective of this presentation is to describe a participatory process to derive collaboration metrics that can be used to assess CAB effectiveness. METHODS/STUDY POPULATION: During the 4th and 5th years of the Great Plains IDeA CTR award, we used a mixed-methods approach that included CAB (1) discussions related to the need to assess collaboration effectiveness, (2) review of the validated Wilder Collaboration Inventory to identify factors that, if maximized, would improve a sense of team science and enhance productivity, (3) planning for assessment frequency and follow-up processes, and (4) review of collaboration data to determine necessary actions for improvement. Qualitative data were gathered across components of the mixed-methods approach. Quantitative data were collected and reviewed by the CAB (n=11 members) during the 1st quarter of award year 5. RESULTS/ANTICIPATED RESULTS: CAB members expressed an interest in assessing collaboration effectiveness, identified important factors to assess, and agreed that annual assessment and follow-up would be appropriate. Key factors identified and assessed (5-point agreement scale--higher score reflects stronger agreement) were 1) mutual respect/trust (m=4.2); 2) appropriate cross section of members (m=3.6); 3) a shared stake in the process and outcomes (m=3.9); 4) flexibility in decision-making/collaboration (m=4.1); 5) roles and policy guidelines (m=3.6); 6) open communication (m=3.9); 7) goal achievement (m=4.0); 8) shared vision (m=4.0); and 9) skilled leadership (m=4.4). DISCUSSION/SIGNIFICANCE OF FINDINGS: CAB reflection on the initial collaboration assessment resulted in developing plans to broaden membership and clarify roles and policy guidelines related to CAB participation. There was strong consensus related to the utility of this assessment approach.

Transdisciplinary Translational Science for Youth Health and Wellness: Introduction to a Special Issue

BackgroundTransdisciplinary translational science applies interdisciplinary approaches to the generation of novel concepts, theories and methods involving collaborations among academic and non-academic partners, in order to advance the translation of science into broader community practice.ObjectiveThis paper introduces a special issue on transdisciplinary translational science for youth health and wellness. We provide an overview of relevant research paradigms, share the related goals of the Iowa State University Translational Research Network (U-TuRN), and introduce the specific papers in the issue.MethodAuthors were asked to submit empirical reports, programmatic reviews or policy-related papers that examined youth health issues from a transdisciplinary translational perspective.ResultsThe papers included in this special issue each involve direct and fully-integrated community-university partnerships and collaborations between academic and non-academic partners in scholarship and research. Reports emphasize the value of the applied nature of the work with a research agenda driven primarily by real-world health and social needs.ConclusionsThere is growing acceptance of the need for transdisciplinary, community-university collaborative research approaches as a means to meet both the requirements posed by real-world problems as well as goals of advancing scientific knowledge and innovation. In this issue, readers will find papers that show the promise of rethinking existing conceptual frameworks to incorporate transdisciplinary approaches as a catalyst to addressing translational science questions related to the field of children and youth care.

Utilizing a Social-Ecological Health Promotion Framework to Engage Diverse Populations for Recruitment in the All of Us Research Program

In 2017, the National Institutes of Health (NIH) All of Us Research Program announced a funding opportunity for community partners to “educate, motivate, and facilitate enrollment” of volunteers. In response to this opportunity, four institutions from the Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN) formed the Precision Medicine Research (PreMeR) Diversity Consortium. This multi-institutional collaboration proposed to employ evidence-based best practices to engage, recruit, and retain diverse populations in the All of Us program. The PreMeR approach was premised on the notion that engagement, recruitment, and retention strategies in community and biomedical research must be viewed as community-engaged public health interventions and utilize the same theoretical principles and approaches. To that end, social influence theories were key in conceptualizing approaches to engaging diverse populations in research, as they helped PreMeR members better understand how people’s beliefs and opinions could be modified to effect change and lead to action (Stokols, 1996). PreMeR adopted the social-ecological model (SEM) for health promotion (Dahlberg & Krug, 2006) from Stokols (1996) and community-based participatory research (CBPR) models (Israel et al., 1998, 2005; Wallerstein & Duran, 2010) to guide proposed engagement, recruitment, and retention strategies. The processes of contextualizing engagement strategies across the individual, interpersonal, organizational, community, and policy spheres of influence necessitated the incorporation of multiple methods to reach diverse audiences. This article provides a model for applying a theory-driven approach to research engagement, recruitment, and retention.

Community-engaged research in translational science: Innovations to improve health in Appalachia.

Health disparities between Appalachia and the rest of the country are widening. To address this, the Appalachian Translational Research Network (ATRN) organizes an annual ATRN Health Summit. The most recent Summit was held online September 22-23, 2020, and hosted by Wake Forest Clinical and Translational Science Institute in partnership with the Northwest Area Health Education Center. The Summit, titled "Community-Engaged Research in Translational Science: Innovations to Improve Health in Appalachia," brought together a diverse group of 141 stakeholders from communities, academic institutions, and the National Center for Advancing Translational Science (NCATS) to highlight current research, identify innovative approaches to translational science and community-engaged research, develop cross-regional research partnerships, and establish and disseminate priorities for future Appalachian-focused research. The Summit included three plenary presentations and 39 presentations within 12 concurrent breakout sessions. Here, we describe the Summit planning process and implementation, highlight some of the research presented, and outline nine emergent themes to guide future Appalachian-focused research.

Participatory needs assessment and action planning for a clinical and translational research network.

The goal of this study was to assess the utility of participatory needs assessment processes for continuous improvement of developing clinical and translational research (CTR) networks. Our approach expanded on evaluation strategies for CTR networks, centers, and institutes, which often survey stakeholders to identify infrastructure or resource needs, using the case example of the Great Plains IDeA-CTR Network. Our 4-stage approach (i.e., pre-assessment, data collection, implementation of needs assessment derived actions, monitoring of action plan) included a member survey (n = 357) and five subsequent small group sessions (n = 75 participants) to better characterize needs identified in the survey and to provide actionable recommendations. This participatory, mixed-methods needs assessment and strategic action planning process yielded 11 inter-related recommendations. These recommendations were presented to the CTR steering committee as inputs to develop detailed, prioritized action plans. Preliminary evaluation shows progress towards improved program capacity and effectiveness of the network to respond to member needs. The participatory, mixed-methods needs assessment and strategic planning process allowed a wide range of stakeholders to contribute to the development of actionable recommendations for network improvement, in line with the principles of team science.

Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

Simple SummaryData about the efficacy of trastuzumab emtansine (T-DM1) following pertuzumab treatment is limited due to the simultaneous development of the two drugs. Thus, the aim of this study was to investigate the efficacy of T-DM1 after previous treatment with pertuzumab in a large, real-world group of patients. We showed that the progression-free survival (PFS) in patients treated with T-DM1 after pertuzumab was 3.5 months. T-DM1 was mainly administered second-line after pertuzumab. The PFS in higher therapy lines appears to be shorter than in second-line ones. In summary, this study provides evidence that T-DM1 has clinically reasonable activity after prior pertuzumab treatment, with a median PFS period of approximately 3–4 months. It appears to be recommendable to administer T-DM1 in earlier therapeutic lines.The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8–7.8); in second-line treatment, 7.7 months (95% CI: 2.8–11.0); in third-line, 3.4 months (95% CI: 2.3–not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2–NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.

What Can Health Services Researchers Offer Health Systems? Developing Meaningful Partnerships Between Academics and Health System Workers Comment on "Experience of Health Leadership in Partnering with University-Based Researchers in Canada - A Call to 'Re-imagine' Research".

As healthcare researchers, we know very well our own experiences on the challenges of partnering with those in the health system to do collaborative, internationally-regarded studies aiming for impact. Bowen and colleagues’ study in Canada empirically examines these issues from the other side, interviewing health system leaders about their perspectives of us researchers, research collaborations and the challenges and opportunities these pose. Based on their findings, they propose a need to re-imagine the contours of research. Inspired by that, in this commentary we examine the context for research partnerships and consider some of the emerging models for fostering more meaningful collaborations between researchers and those working in healthcare systems and organisations. Based on principles of embedded research and researchers, these models—including translational research networks (TRNs) and researcher-in-residence models—rely on a complex interplay of personal and interpersonal factors to be successful.

Northern New England Clinical and Translational Research Network Assesses the Training Needs of Investigators

Northern New England Clinical and Translational Research Network Assesses the Training Needs of Investigators

Establishing a translational research network in the Asia-Pacific Region through Industry-Academia-Government Collaboration: The Japan Medical Innovation Program

Establishing a translational research network in the Asia-Pacific Region through Industry-Academia-Government Collaboration: The Japan Medical Innovation Program

Needle- and Cold Chain- Free Rice-Based Oral Vaccine, MucoRice-CTB Shows Microbiota-Dependent Immunogenicity in Humans

Background: Diarrheal disease remains a global health issue. It is estimated that there are 1.3 to 4.0 million cases of cholera and 20,000 to 140,000 cholera-related deaths worldwide each year. In addition, pandemic diarrhea and travelers’ diarrhea caused by enterotoxigenic Escherichia coli heat-labile enterotoxin (LT) are estimated to affect approximately 200 million and 27 million people, respectively, worldwide each year. Our previous studies showed that rice-based cholera toxin B subunit (CTB) vaccine, MucoRice-CTB is a cold-chain and needle-syringe free oral vaccine candidate which will be benefited to less infrastructure conditions. Methods: We conducted a double-blind, randomized, placebo-controlled, three-cohort, dose-escalation phase I study to evaluate the safety, tolerability, and efficacy of MucoRice-CTB (clinical study code name: IMSUT-MR1501) administered as four oral doses at 2-week intervals to healthy Japanese adults. In addition to vaccine evaluation, metagenomic analysis of study participants was performed by using bacterial DNA from fecal samples. Interpretation: MucoRice-CTB induces cross-reactive antigen-specific antibodies against CTB and B subunit of LT in a dose-dependent manner, without inducing serious adverse events. Antibodies isolated from responders to the vaccine inhibited the binding of CT and LT to GM1 ganglioside receptor and the elongation of Chinese hamster ovary cells caused by the both enterotoxins. Metagenome analysis of subjects’ feces collected prior to the start of vaccination revealed that responders had a gut microbiota of higher diversity that was characterized by larger populations of E. coli and Shigella spp. compared with those in non-responders. Findings: This phase I clinical trial showed that MucoRice-CTB induces neutralizing antibodies against diarrheal toxins in a gut microbiota-dependent manner without major adverse events. Trial Registration: (clinical trial registration: UMI18001) Funding Statement: The costs related to this study are covered by support of the “Translational Research Network Program” of the Ministry of Education, Culture, Sports, Science and Technology. Declaration of Interests: The authors stated that: None of the items involve any conflicts of interest. Ethics Approval Statement: The clinical research protocols were approved and received ethical clearance (permit #27-41- 0917 and #27-48-0128) from the IRB of the Institute of Medical Science, The University of Tokyo (IMSUT), Japan.

Sporadic Inclusion Body Myositis Underling Mitochondrial Dysfunction Ameliorated by Mitochondrial Homing Drug, MA-5

Background: Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and mitochondrial abnormalities may be involved. Methods: We recruited 9 sIBM patients and we examined mitochondrial functions with bioenergetic and examinations and dynamics of patient myoblasts with measuring a mitochondrial disease marker growth differential factor 15 (GDF15). We also examined the effect of a new candidate drug, Mitochondria acid-5 (MA-5). Findings: Bioenergetic analysis of sIBM patient myoblasts revealed damaged mitochondrial function with decreased ATP, mitochondrial size and impaired mitochondrial dynamics and cell vulnerability. MA-5 increased the ATP level and reduced mitochondrial ROS, following the protection against cell death. The reduced levels of Opa1 and Drp1 showed the impairment of mitochondrial fusion/fission process and that MA-5 ameliorated. Skin fibroblasts from sIBM patients can be used for diagnosis. Interpretation: GDF15 and MA-5 could provide both a new maker and therapeutic strategy for sIBM patients. Funding Statement: These works were supported in part by National grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18H02822), Translational Research Network Program (C50) from Japan Agency for Medical Research and Development (AMED). MEXT and AMED, JAPAN. Declaration of Interests: The authors state: None. Ethics Approval Statement: Myoblasts and fibroblasts obtained by muscle and skin biopsy of sIBM patients were collected in Tohoku University Hospital under the approval of the Ethical Committee of Tohoku University.

Automated Reports for Monitoring and Improving Data Quality in a Translational Research Network.

Standardised, automated quality reports were generated at three pilot locations of the decentralized translational research network DKTK with separated local data warehouses (LDW), for assessing syntactic conformity against common data element definitions deposited in a central metadata repository (MDR). Deviations in the LDW were categorised, and locally corrected. Comparisons of reports from two time points confirm a major improvement in data quality in terms of syntactic conformity, an essential prerequisite for network-wide data integration.

SAT-LB050 Congenital Adrenal Hyperplasia Newborn Screening Protocols Differ Widely in the US: A Survey by the Differences/Disorders of Sex Development Translational Research Network (DSD-TRN)

All 50 United States and the District of Columbia incorporate newborn screening for congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency. Filter paper blood specimens are typically collected in full-term infants on day two of life for 17-hydroxyprogesterone (17OHP) fluoroimmunoassay (DELFIA). Prematurity, low birth weight, or critical illness are known to cause falsely elevated results. Protocols differ for each state laboratory as to assay cut-points by birthweight or gestational age, which are key in determining the positive predictive value. As a preliminary step to quality improvement, we investigated the diversity of approaches to CAH screening nationally among the states representing members of the DSD-Translational Research Network. Ten data sets were returned from a survey circulated to state laboratory directors with qualitative and quantitative information about individual screening programs. Disease incidence generally correlated with published worldwide data, ranging from 1:10,000 to 1: 28,500 live births. Screening results are typically reported by direct phone call to the designated healthcare provider and/or coordinator at each referral center, followed by a faxed written report. Specialists are notified of unequivocally high 17OHP results; however, borderline results are not usually referred to a pediatric endocrinologist. Only one state laboratory required a mandatory second screen for healthy term infants regardless of initial screen result; most did for infants in intensive care units. Nine of 10 programs utilized birthweight cut-points, but cutoffs for normal results varied widely - from 17OHP values of 25 to 75 ng/mL for birthweights >2250-2500 grams. One program used gestational age cut-points. The positive predictive values for term or normal birthweight infants varied from 1.2 to 9.6%, implying differences in sensitivity and/or specificity of screening between states. There was no apparent correlation between the total number of infants each state screened annually, assay cut-point and positive predictive value. Data were unavailable for negative predictive values. Conclusion: There is a need for standardization of newborn screening protocols for CAH to improve the positive predictive value. Future efforts will be directed to expanding this survey and determining best practices. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

3369 Assessment to Action: Engaging network member’s in identifying needs and directions of network improvement

OBJECTIVES/SPECIFIC AIMS: To complete a needs assessment and action planning process that engaged clinical and translational research network members in identifying needs through survey feedback, characterizing the needs in small group sessions, and developing recommendations for action at the network’s annual scientific meeting. METHODS/STUDY POPULATION: The project included (1) a survey of 357 members across partner institutions from the Great Plains IDeA CTR Network, (2) 6 - 90 minute brainstorming sessions to characterize needs identified through survey assessment, and (3) 6 - 60 minute sessions to develop recommendations for network improvement based on the characterization activity. Approximately 75 members participated in the characterization and recommendation sessions. RESULTS/ANTICIPATED RESULTS: Seven areas of need from the survey were identified based upon the frequency of identification by network members (support to move research across the translational spectrum, database design and management, data access and sharing, data analysis, recruitment and retention of subjects, support for members who have submitted grants but were repeatedly unsuccessful, mentoring). Members indicated which characterization sessions they were interested in attending and based on the enrollment numbers needs related to unsuccessful grant submitters and mentoring were combined as were needs related to database design and data access-sharing. Sessions resulted in 8 inter-related recommendations for network action that included to (1) develop GP-CTR directory/registry of clinicians, researchers, system partners, that can be used to identify people that want to be involved in research partnerships or mentoring, (2) create a GP CTR Navigators Program to will provide support to network members throughout the collaborative research and grant preparation process, (3) identify and disseminate information about assets (funding, databases/registries) that exist amongst network partners that can be leveraged by member, (4) develop a searchable repository of evidence-based interventions for T3/T4 efforts, (5) review GP CTR supported professional development, and technological resource offerings and identify potential gaps, (6) facilitate opportunities for peer support/networking, (7) provide guidance to GP CTR network institutions looking to adopt policies that will support translational research collaboration, and (8) identify potential barriers to GP CTR network engagement (i.e., infrastructure, communication, marketing). DISCUSSION/SIGNIFICANCE OF IMPACT: This process allowed for a wide range of network members to contribute to actionable recommendations for CTR leadership to move into action and improve the scientific network’s ability to conduct clinical and translational research.